02.27.09: Water Balance

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02.27.09: Water Balance

  1. 1. Author(s): Roger Grekin, M.D., 2009License: Unless otherwise noted, this material is made available under the terms ofthe Creative Commons Attribution–Noncommercial–Share Alike 3.0 License:http://creativecommons.org/licenses/by-nc-sa/3.0/We have reviewed this material in accordance with U.S. Copyright Law and have tried to maximize your ability to use,share, and adapt it. The citation key on the following slide provides information about how you may share and adapt thismaterial.Copyright holders of content included in this material should contact open.michigan@umich.edu with any questions,corrections, or clarification regarding the use of content.For more information about how to cite these materials visit http://open.umich.edu/education/about/terms-of-use.Any medical information in this material is intended to inform and educate and is not a tool for self-diagnosis or areplacement for medical evaluation, advice, diagnosis or treatment by a healthcare professional. Please speak to yourphysician if you have questions about your medical condition.Viewer discretion is advised: Some medical content is graphic and may not be suitable for all viewers.
  2. 2. Citation Key for more information see: http://open.umich.edu/wiki/CitationPolicyUse + Share + Adapt { Content the copyright holder, author, or law permits you to use, share and adapt. } Public Domain – Government: Works that are produced by the U.S. Government. (17 USC §105) Public Domain – Expired: Works that are no longer protected due to an expired copyright term. Public Domain – Self Dedicated: Works that a copyright holder has dedicated to the public domain. Creative Commons – Zero Waiver Creative Commons – Attribution License Creative Commons – Attribution Share Alike License Creative Commons – Attribution Noncommercial License Creative Commons – Attribution Noncommercial Share Alike License GNU – Free Documentation LicenseMake Your Own Assessment { Content Open.Michigan believes can be used, shared, and adapted because it is ineligible for copyright. } Public Domain – Ineligible: Works that are ineligible for copyright protection in the U.S. (17 USC § 102(b)) *laws in your jurisdiction may differ { Content Open.Michigan has used under a Fair Use determination. } Fair Use: Use of works that is determined to be Fair consistent with the U.S. Copyright Act. (17 USC § 107) *laws in your jurisdiction may differ Our determination DOES NOT mean that all uses of this 3rd-party content are Fair Uses and we DO NOT guarantee that your use of the content is Fair. To use this content you should do your own independent analysis to determine whether or not your use will be Fair.
  3. 3. Water Balance M2 – Endocrine Sequence R. GrekinWinter 2009
  4. 4. POSTERIOR PITUITARY•  Derived from neural tissue.•  Infundibulum and posterior pituitary are primarily nonmyelinated nerve fibers.•  Originate in the supraoptic and paraventricular nuclei
  5. 5. Source Undetermined
  6. 6. ADH STRUCTURE AND SYNTHESIS•  Nine amino acid peptide, sometimes termed arginine vasopression or AVP.•  Synthesized in cell bodies of hypothalamic nuclei as large prohormone.•  ADH and the prohormone are packaged in secretory vesicles and transported to nerve terminals in the stalk and posterior pituitary.•  The large prohormone, termed neurophysin, appears to play an important role in neural transport.
  7. 7. Source Undetermined
  8. 8. MECHANISM OF ADH SECRETION •  Stimulation of hypothalamic nuclei results in axon potentials to the posterior pituitary. •  Resultant calcium influx mediates exocytosis of secretory granules.
  9. 9. OSMOLALITY•  Osmoreceptors in third ventricle, outside the blood brain barrier, respond to small change in "effective" osmolality.•  Osmoreceptor stimulation results in stimulation of ADH producing cells and release of ADH.
  10. 10. OSMOLALITY•  Normal individuals have an osmotic threshold between 280 and 285 mosm/L. •  When plasma osmolality is below threshold, ADH is not secreted. •  Above threshold, ADH secretion is proportional to the increase in osmolality.•  Under most circumstances, osmolality is the only important regulator of ADH secretion.
  11. 11. Source Undetermined
  12. 12. BLOOD VOLUME AND ARTERIAL PRESSURE •  Decreased activity of low pressure or high pressure receptors can trigger secretion of ADH. •  Usually this only happens after substantial changes in blood pressure or volume. •  When baroreceptor stimuli are present, they override the effects of osmolality.
  13. 13. Source Undetermined
  14. 14. Source Undetermined
  15. 15. STIMULATORS OF ADH SECRETION•  Emesis•  Stress•  Drugs
  16. 16. ADH IN CIRCULATION•  Circulates in an unbound form•  Short half life (4-8 minutes)
  17. 17. RENAL ACTIONS OF ADH•  Renders collecting duct permeable to water•  Increases sodium reabsorption in the thick ascending limb of Henle
  18. 18. Source Undetermined
  19. 19. VASCULAR ACTIONS OF ADH •  Potent vasoconstrictor •  Vasoconstrictive effects are probably only important in states of severe hypovolemia or hypotension.
  20. 20. CELLULAR ACTIONS OF ADH •  V1 receptors mediate vascular smooth muscle effects •  V2 receptors are present in renal tubular cells. Their effects are mediated by cAMP
  21. 21. CELLULAR ACTIONS OF ADH •  Aquaporins are membrane proteins that act as water channels. •  ADH stimulates translocation of aquaporin to the membrane of collecting duct cells.
  22. 22. Source Undetermined
  23. 23. dDAVP•  Synthetic ADH like agent used to treat patients with ADH deficiency.•  Binds to V2 receptors, but not to V1 receptors.
  24. 24. THIRST•  Thirst centers are located in the hypothalamus, near the supraoptic and paraventricular nuclei•  Respond to stimulation of osmoreceptors•  Increased osmolality is a potent thirst stimulator
  25. 25. THIRST•  Decreased osmolality does not appear to suppress thirst•  Decreased baroreceptor stimulation increases thirst•  Angiotensin II, within the brain, is a mediator of increased thirst center activity
  26. 26. WATER FOLLOWS SALT
  27. 27. RESPONSE TO WATER DEPLETION•  Osmolality rises (less water than salt)•  Thirst and ADH are stimulated•  Increased water intake and decreased water excretion restore osmolality to normal
  28. 28. RESPONSE TO WATER EXCESS •  Osmolality falls •  ADH secretion is suppressed (thirst is usually not suppressed) •  Renal water excretion is increased
  29. 29. OXYTOCIN: SYNTHESIS AND SECRETION •  Nine amino acid peptide, all but two amino acids are the same as ADH. •  Synthesis and storage are identical to ADH •  Oxytocin has a different neurophysin than ADH.
  30. 30. Source Undetermined
  31. 31. SECRETION OF OXYTOCIN•  Suckling•  Uterine stretch
  32. 32. MILK LET DOWN•  Milk secretion requires contraction of myoepithelial cells lining alveoli•  Oxytocin simulates contraction of myoepithelial cells, without it, lactation does not occur
  33. 33. PARTURITION•  At the end of pregnancy, myometrium is highly sensitive to oxytocin•  As labor progresses, increasing oxytocin levels cause uterine contraction•  Postpartum, oxytocin induced myometrial contraction is important in minimizing blood loss•  Oxytocin is sometimes used to induce labor
  34. 34. A 25 year old man had the sudden onset ofmarked polyuria and polydipsia. He neverslept for more than 2-3 hours at a time,spending much of the night in the bathroom.Except for some fatigue, he felt well, with noother symptoms.
  35. 35. Routine labs revealed:Na = 142 mEq/l (137-144)K = 3.8 mEq/l (3.6-5.0)Cl = 100 mEq/l (95-102) HCO3 = 29 mEq/l (25-31) BUN = 18 mg/dl (0-20) Creat = 1.2 mg./dl (0-1.4)Plasma osmolality = 286 mosm/l(278-288)Urine osmolality = 68 mosm/l24 hour Urine volume = 9540 ml
  36. 36. Plasma Osm Urine Osm Basal 285 64 1 hr 59 2 hr 67 3 hr 82 4 hr 294 74 5 hr 301 77DdAVP administered 6 hr 352 7 hr 504
  37. 37. He was treated with desmopressin (DdAVP),0.1 mg twice daily. Thirst and frequency ofurination returned to normal.
  38. 38. DIABETES INSIPIDUSThe clinical manifestation of ADH deficiency
  39. 39. ETIOLOGY OF DIABETES INSIPIDUS•  Trauma•  Neoplasm•  Idiopathic•  Familial•  Other pituitary and hypothalamic lesions
  40. 40. PATHOPHYSIOLOGY OF DIABETES INSIPIDUS•  In the absence of ADH, patients are unable to concentrate urine, even when there is water deprivation and hyperosmolality•  As water deprivation occurs, it constitutes a potent stimulus for thrist•  Otherwise healthy patients are able to maintain normal osmolality by drinking large amounts
  41. 41. SYMPTOMS OF DIABETES INSIPIDUS•  Marked polyuria and polydipsia•  Usually not dehydrated as long as they are conscious and thirst center is intact•  If access to water is limited, hypernatremia rapidly occurs
  42. 42. WATER DEPRIVATION TEST•  Normals will increase urine osmolality to 800 mOsm/L•  After urine osmolality has plateaued, inject dDAVP if levels are less than 800 mOsm/L•  In borderline cases, measurement of ADH after water deprivation is helpful.
  43. 43. WATER DEPRIVATION TEST•  Pituitary DI: unable to concentrate urine despite hyperosmolar serum. After dDAVP injection, Uosm increases.•  Nephrogenic DI: unable to increase urine osmolality after water deprivation and after dDAVP.•  Primary polydipsia: should concentrate urine normally following water deprivation
  44. 44. NEPHROGENIC DIABETES INSIPIDUS•  Familial•  Renal disease•  Hypercalcemia•  Hypokalemia•  Lithium therapy
  45. 45. A 61 year old man was admitted to the VAHospital for evaluation of convulsions. Hehad been well until 3 months beforeadmission when he developed anorexia andnausea. He lost 14 lbs in the 3 months beforeadmission. Two weeks before admission hebecame confused, and his wife noted he wasunable to dress himself. The confusionimproved, but he then had two generalizedconvulsions in the three days beforeadmission.
  46. 46. Physical examination revealed a cachecticappearing man. Weight 137; height 511".Blood pressure 115/75, pulse 92 and regular.He was oriented to person and place but not totime. He could not name the president norsubtract 7 from 100. Proverb interpretationwas concrete. The rest of the neurologic examwas normal.
  47. 47. Na = 109 mEq/l (137-144) K = 3.7 mEq/l (3.6-5.0) Cl = 84 mEq/l (95-102) HCO3 = 20 mEq/l (24-31) BUN = 4 mg/dl (6-20) Creat = 0.8 mg/dl (0-1.4) Plasma osmolality = 232 mosm/l (278-288) Urine osmolality = 552 mosm/l
  48. 48. Chest film: 3 cm right hilar massHe was treated with a 500 ml per day waterrestriction, with a rise in serum Na to 129 andmarked improvement in mental status.
  49. 49. CT scan demonstrated mediastinal metastases.He was treated with chemotherapy, butattempts to liberalize his fluid intakeconsistently resulted in recurrenthyponatremia. Demeclocycline was added tohis regimen, and serum sodium ranged from124 to 135 mEq/l without water restriction.
  50. 50. SYNDROME OF INAPPROPRIATE ADH (SIADH) Secretion of ADH despite water retention and plasma hypotonicity
  51. 51. ETIOLOGY OF SIADH•  CNS disorders•  Malignant tumors secreting ADH•  Pulmonary disease•  Drugs
  52. 52. PATHOPHYSIOLOGY OF SIADH •  Drinking continues despite inability to dilute urine and excrete excess water •  Volume expansion and hypotonicity ensue •  New steady state is attained, but only after significant water retention has occurred
  53. 53. SYMPTOMS OF SIADH•  Na>120, patients are usually asymptomatic•  Na between 110 and 120, confusion and lethargy may occur•  Na<110, convulsions, coma, and death may result•  Rate of fall of Na is more important than the absolute level
  54. 54. DIAGNOSIS OF SIADH (PART 1) •  Hypotonic, hyponatremic plasma, with inappropriately hypertonic urine. •  Usually urine osmolality is greater than serum osmolality. •  Exclude other causes of hyponatremia – Hyperglycemia – Hyperlipidemia
  55. 55. DIAGNOSIS OF SIADH (PART 2) •  Evaluate for conditions known to stimulate ADH secretion. – Volume depletion – Heart failure – Cirrhosis – Nephrotic syndrome – Hypothyroidism – Cortisol deficiency
  56. 56. TREATMENT OF SIADH•  Acutely ill patients should receive hypertonic saline. Furosemide may be added to promote water excretion•  Conivaptan, an intravenous ADH V2 receptor antagonist, promotes water excretion and increases osmolality•  Excessively rapid correction of hyponatremia can cause brain stem damage and should be avoided
  57. 57. CHRONIC TREATMENT OF SIADH•  Treat underlying disorder•  Water restriction•  Drugs which cause nephrogenic diabetes insipidus: Demeclocycline•  Oral ADH antagonists are under development
  58. 58. Additional Source Information for more information see: http://open.umich.edu/wiki/CitationPolicySlide 5: Source UndeterminedSlide 7: Source UndeterminedSlide 11: Source UndeterminedSlide 13: Source UndeterminedSlide 14: Source UndeterminedSlide 18: Source UndeterminedSlide 22: Source UndeterminedSlide 30: Source Undetermined

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